Down Syndrome and Acute Leukemia: Epidemiological and Genetic Relationships Lawrence W. Powers, PhD, MT(ASCP), and Michelle K. Register, BS

Children with Down syndrome (DS) demonstrate increased risk for acute leukemia. Although the incidence of acute lymphoblastic leukemia is the same in children with and without DS, the rate of occurrence of acute myelogenous leukemia (AML) is increased in children with DS younger than 3 years. Many cases of undifferentiated and blastic leukemias, examined by newer procedures, appear to be acute megakaryoblastic leukemia (AMKL), Fab-M7. Transient leukemoid reaction (TLR), a neonatal phenomenon with many of the features of acute leukemia, also occurs most frequently in children with DS. Although TLR typically remits without treatment, some patients with TLR subsequently develop a true acute leukemia. The relationships between DS, TLR, congenital leukemia, and the various forms of AML are not well understood. Hematological, epidemiological, and cytogenetic evidence linking these phenomena are reviewed and discussed. From the Department of Medical Technology, University of South Alabama, Springhill Ave Campus, Mobile, Ala. Reprint requests to the Department of Medical Technology, University of South Alabama, 1504 Springhill Ave, Rm 2309, Mobile, AL 36604 (Dr Powers).

630

own syndrome (DS) results from abnormalities involving chromosome 21, the smallest of the autosomes. The characteristic appearance and associated mental retardation of DS was described in 1866 by John Langdon Down. Children display varying degrees of the following: a flattened face, prominent epicanthal folds (responsible for the inappropriate designation of "mongolism"), protruding furrowed tongue, speckled irises (Brushfield spots), and dysplastic ears. Mental retardation may be mild to severe, with IQ scores frequently less than 50. Most children show some degree of growth retardation as well. It is the most common chromosomal abnormality, occurring in about 1 of 700 live births. However, approximately 60% of embryos with these abnormalities are aborted spontaneously and 20% of fetuses are stillborn; thus the incidence of DS at conception is closer to 1 in 140. In the past, 30% of these children died within 1 year after birth, 50% within 5 years, and only 8% of individuals with DS were expected to reach 40 years of age.1 Although medical intervention has improved these survival figures, serious complications remain, including various cardiac anomalies and an increased risk of malignancy.

Laboratory Medicine Vol. 22, No. 9 September 1991

Acute leukemia (AL) is a rapidly progressing neoplasm of the hematopoietic tissue characterized by proliferation and maturation arrest of one or more blood cell lines. Various factors are known to be associated with the onset of AL in humans, including (1) exposure to ionizing radiation or certain toxic chemicals, (2) infection by the retrovirus, HTLV-I, and (3) alterations of genetic instructions that may be related to various chromosome abnormalities. The latter is of particular interest because of the role that genetic factors may play in the etiology of cancer and the epidemiological evidence that associates particular chromosome changes with specific neoplasms. This review examines some of the epidemiological and cytogenetic evidence for links between DS, acute leukemia, and transient leukemoid reaction (TLR), a controversial neonatal phenomenon.

~ pidemiology — Risk factors for DS have been — studied extensively and consideration has been given to maternal age, paternal age, birth order, geographical location, season of birth, race, environmental exposure to radiation, chemicals, oral contraceptives, spermicides, fluoride in water, viral agents,

the French-American-British (FAB) system of leukemia classification based on standardized protocols.

80 % Live Births % DS Cases

C

60 o c ,

73 =3

to o

1

2 3-6 Patient Age, y

80

7-9

10-18

DS—ANLL % With DS (n=20)

a. 2

60

% Without DS(n=931)

a >>

1 40 20